The maintenance of cardiac performance would be of positive survival value in various forms of circulatory shock states. A circulating cardiodepressant factor, termed myocardial depressant factor (MDP), has been hypothesized to be the pathogenic agent for cardiac dysfunction in shock states. This hypothesis remains one of the most controversial hypotheses explaining the cardiovascular collapse of irreversible circulatory shock. This cardiodepressant peptide apparently originates in the ischemic pancreas, but its actions and role have remained controversial. This project seeks to define the pathophysiological role of this factor in the development of irreversible shock. This will necessitate the isolation, purification, and structural analysis of the factor(s) that possess MDF-like activity. Preliminary results in our laboratory indicate the existence of such pancreatic material and suggest the active component is a single moiety rather than a group. We have also been able to partially isolate this material by use of a cellulose column. The quantification of the biological actions of the purified factor will be assessed in the isolated papillary muscle, isolated purified heart, and in vivo. In order to ascertain the role of the compound in the pathogenesis of circulatory shock, a specific antibody against the compound will be formed and administered to a variety of shock models. By selectively removing the MDF-like compound from the circulation in a variety of shock states, it should be possible to definitely ascertain the role of the compound with MDF activity in the development of irreversible shock. Using this approach, it may be possible to obtain data upon which a rational evaluation of the pathogenic role of MDF in the genesis of circulatory shock may be made.